DESCRIPTION: The goal of this application is to understand at a molecular level the interactions that dictate peptide binding and presentation by class I major histocompatability complexes (MHC) and to identify the features of T cell receptor (TCR) involved in recognizing these peptides in the context of the MHC. Crystal structures will be determined for a group of murine MHCs complexed with peptide antigens to probe the binding of different-length peptides, to visualize a proposed intermediate that may trap an open form of the MHC, and to establish the basis for peptide specificity of MHCs in the L locus. A very convenient bacterial expression system for production of mg quantities of pure MHC bound to a single synthetic peptide is being used for this work. Crystal structures for three TCRs in complex with peptide-bound MHCs will also be determined. The focus of these experiments is to determine what allows the TCR to recognize foreign peptides as presented by MHCs. Substantial preliminary results, including purified materials, crystals, diffraction data and, in some cases, structures, are available for all components of the project.